In the first experiment, the applicant will have available to him blood samples for measurement of various adrenal hormones (corticosterone, aldosterone, DOC, androstenedione, DHA, and ACTH). These will be obtained after decapitation at which time the adrenal glands wll be removed along with the pituitary for in vitro assessment of function. The pituitary will be challenged with a commercial preparation of CRF, and ACTH will be measured. A portion of the adrenal (left adrenal) will be challenged with graded doses of ACTH. Corticosterone, aldosterone, DOC, DHA and androstenedione levels will be assessed from the media of the superfusate. The right adrenal will be weighed and prepared for histologic examination. Morphometric analysis will be carried out for determination of the cell number of each zone. Lipofuscin content and relative disorganization of the columnar structure will be made for one group of animals. Parallel studies of this type will be performed on animals exposes to acute ether stress or avoidable foot shock; in vitro experiments will not be run on these animals. In the second experiment, hormone levels will be determined in young (Y), middle-aged (M), and old (O) animals that were exposed to 7 months of chronic stress (shock avoidance, 4 hours/day, 7 days/week) and then allowed to remain in an unstressed condition for an additional month before sacrifice. In a subgroup of animals similarly treated, pituitary tissue and adrenals will be assessed in vitro. Histological examination of the tissue will be made. In the third experiment, the M group of animals will be used to look at effects of stress at 2 weeks, and 2, 4, and 7 months after shock avoidance stress. In vitro characterization of the adrenal axis will be made, and histological analysis will be performed. In the fourth experiment, more precise analysis will be made of the nature of the changes which have occured in the aged and stress-aged animals. In vivo studies with cannulated animals will be initiated. The fifth experiment consists of studies conducted in the fourth and fifth years that are designed to understand the causative factors responsible for the stress-induced aging changes. Pharmacologic agents that block the endogenous opioid peptides (naltrexone)and catecholamines will be used in order to determine which of the stress-related changes are due to involvement of the opioid or catecholamine systems. Lastly, corticosterone will be administered to unstressed animals in a manner which mimics the levels seen during shock avoidance stress to determine the role of the steroid in causing the advancement of age-related changes.